A method of using an aldehyde and p-tolylsulfonylmethylisocyanide (hereinafter abbreviated as TosMIC) is generally known as a particularly useful process among those for synthesizing 5-substituted oxazole compounds. Generally, the process involves reacting an aldehyde with TosMIC in methanol in the presence of potassium carbonate. In addition, another known method involves the reaction in dimethoxyethane and methanol in the presence of an ion exchange resin (Ambersep 9000H-) (Tetrahedron Letters, 1972, 2369; Lect Heterocycl. Chem., 1980, (5), SI 11–122; Tetrahedron Letters, 1999, 5637–5638, and others).
Methods for synthesizing 5-substituted imidazoles with TosMIC are also known. Generally, an imino compound is reacted with TosMIC in an alcohol-type solvent in the presence of potassium carbonate (Tetrahedron Letters, 1976, 143–146; J. Org. Chem., Vol. 42 (7), 1997, 1153–1159; Tetrahedron Letters, 2000, 5453–5456; and Tetrahedron, 53 (6), 2125–2136, 1997).
In all of the said processes, TosMIC is handled as crystals. Because of this, complicated isolation procedures including concentration, crystallization, separation of solvents, and drying are required, depending on the conditions, when the compound is produced industrially. Besides, a decrease in TosMIC production yield is unavoidable due to loss of product in filtrates. Furthermore, TosMIC is irritating, unstable and explosive with a low decomposition point. Its isolation should be avoided for safety reasons.
As described above, it is preferable not to isolate TosMIC when safety is taken into account. To handle TosMIC without isolating it, it is inevitable to use the reaction solution itself or a solution of another extract solvent after TosMIC is synthesized and post-treatments are done. It has been essential to develop safer processes for producing 5-substituted oxazoles and 5-substituted imidazoles with TosMIC in a solution without isolating it.